tbuckley/cabot-search huggingface dataset:
Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs
Authors: Ran Qi, Yixuan Bai, Kun Li, Nanbin Liu, Yan Xu, Emre Dal, Yufeng Wang, Rui Lin, Hui Wang, Zhongyan Liu, Xinbo Li, Xiuyan Wang, Baomin Shi
Journal: Drug Resistance Updates (2023)

Pancreatic cancer continues to be one of the world's most lethal cancers. Chemotherapy resistance in patients with advanced pancreatic cancer often accompany with dismal prognosis, highlighting the need to investigate mechanisms of drug resistance and develop therapies to overcome chemoresistance.This research was filed with the Chinese Clinical Trial Registry (ChiCTR2200061320). In order to isolate primary normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) samples of pancreatic ductal adenocarcinoma (PDAC) and paracancerous pancreatic tissue from individuals diagnosed with PDAC were obtained. The exosomes were obtained using ultracentrifugation, and their characteristics were determined by Western blotting, nanoparticle tracking analysis, and transmission electron microscopy. CAF-derived miRNAs were analyzed by RT-qPCR and high-throughput sequencing. Gemcitabine (GEM) was employed to promote ferroptosis, and ferroptosis levels were determined by monitoring lipid reactive oxygen species (ROS), cell survival, and intracellular Fe2+ concentrations. To assess in vivo tumor response to GEM therapy, a xenograft tumor mouse model was utilized.Exosomes derived from CAFs in PDAC did not exhibit innate GEM resistance. CAFs promoted chemoresistance in PDAC cells following GEM treatment by secreting exosomes, and maintaining signaling communication with cancer cells. Mechanistically, miR-3173-5p derived from CAF exosomes sponged ACSL4 and inhibited ferroptosis after uptake by cancer cells.This work demonstrates a novel mode of acquired chemoresistance in PDAC and identifies the miR-3173-5p/ACSL4 pathway as a promising treatment target for GEM-resistant pancreatic cancer.
PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1
Authors: Fei Xie, Han Zhang, Kongkai Zhu, Cheng‐Shi Jiang, Xiaoya Zhang, Hongkai Chang, Yaya Qiao, Mingming Sun, Jiyan Wang, Mukuo Wang, Junzhen Tan, Tao Wang, Lianmei Zhao, Yuan Zhang, Jianping Lin, Chunze Zhang, Shuangping Liu, Jianguo Zhao, Cheng Luo, Shuai Zhang, Changliang Shan
Journal: MedComm (2023)

Abstract Protein arginine methyltransferase 5 (PRMT5) is a major type II enzyme responsible for symmetric dimethylation of arginine (SDMA), and plays predominantly roles in human cancers, including in ovarian cancer. However, the exactly roles and underlying mechanisms of PRMT5 contributing to the progression of ovarian cancer mediated by reprogramming cell metabolism remain largely elusive. Here, we report that PRMT5 is highly expressed and correlates with poor survival in ovarian cancer. Knockdown or pharmaceutical inhibition of PRMT5 is sufficient to decrease glycolysis flux, attenuate tumor growth, and enhance the antitumor effect of Taxol. Mechanistically, we find that PRMT5 symmetrically dimethylates alpha‐enolase (ENO1) at arginine 9 to promotes active ENO1 dimer formation, which increases glycolysis flux and accelerates tumor growth. Moreover, PRMT5 signals high glucose to increase the methylation modification of ENO1. Together, our data reveal a novel role of PRMT5 in promoting ovarian cancer growth by controlling glycolysis flux mediated by methylating ENO1, and highlights that PRMT5 may represent a promising therapeutic target for treating ovarian cancer.
Human Mpox Virus Infection After Receipt of Modified Vaccinia Ankara Vaccine—Reply
Authors: Aniruddha Hazra, John A. Schneider
Journal: JAMA (2023)

In Reply In response to our Research Letter1 on mpox infection in the immediate period following vaccination with MVA-BN, Dr Zhou raises 2 important concerns about how to better assess vaccine effectiveness of MVA-BN against mpox.
Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer
Authors: Julie E. Bauman, Nabil F. Saba, Denise Roe, Jessica R. Bauman, John Kaczmar, Aarti Bhatia, Jameel Muzaffar, Ricklie Julian, Steven Wang, Shethal Bearelly, Audrey Baker, Conor Steuer, Anshu Giri, Barbara Burtness, Sara Centuori, Carlos Caulin, Robert Klein, Kathylynn Saboda, Stefanie Obara, Christine H. Chung
Journal: Journal of Clinical Oncology (2023)

Primary or acquired resistance to cetuximab, an antiepidermal growth factor receptor monoclonal antibody (mAb), minimizes its utility in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Aberrant hepatocyte growth factor/cMet pathway activation is an established resistance mechanism. Dual pathway targeting may overcome resistance.This multicenter, randomized, noncomparative phase II study evaluated ficlatuzumab, an antihepatocyte growth factor mAb, with or without cetuximab in recurrent/metastatic HNSCC. The primary end point was median progression-free survival (PFS); an arm met significance criteria if the lower bound of the 90% CI excluded the historical control of 2 months. Key eligibility criteria were HNSCC with known human papillomavirus (HPV) status, cetuximab resistance (progression within 6 months of exposure in the definitive or recurrent/metastatic setting), and resistance to platinum and anti-PD-1 mAb. Secondary end points included objective response rate (ORR), toxicity, and the association of HPV status and cMet overexpression with efficacy. Continuous Bayesian futility monitoring was used.From 2018 to 2020, 60 patients were randomly assigned and 58 were treated. Twenty-seven versus 33 patients were allocated to monotherapy versus combination. Arms were balanced for major prognostic factors. The monotherapy arm closed early for futility. The combination arm met prespecified significance criteria with a median PFS of 3.7 months (lower bound 90% CI, 2.3 months; P = .04); the ORR was 6 of 32 (19%), including two complete and four partial responses. Exploratory analyses were limited to the combination arm: the median PFS was 2.3 versus 4.1 months (P = .03) and the ORR was 0 of 16 (0%) versus 6 of 16 (38%; P = .02) in the HPV-positive versus HPV-negative subgroups, respectively. cMet overexpression was associated with reduced hazard of progression in HPV-negative but not HPV-positive disease (P interaction = .02).The ficlatuzumab-cetuximab arm met significance criteria for PFS and warrants phase III development. HPV-negative HNSCC merits consideration as a selection criterion.
Genomic and Immune Features in an Intrahepatic Cholangiocarcinoma Patient with Microsatellite Instability-High Suffered Rapid Acquired Resistance to PD-1 Inhibitor
Authors: Zhuo Cheng, Tianmei Zeng, Guang Yang, Di Liu, Zhi Zheng, Zhengang Yuan
Journal: Liver Cancer (2023)

Introduction: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver malignancy with poor prognosis. Recently, the development of immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) inhibitors, has emerged as a promising strategy in multiple tumor types, including ICC. Microsatellite instability-high (MSI-H) is an important biomarker for ICIs in solid tumors. The response rate in patients with MSI-H is significantly higher than in those with microsatellite stability/microsatellite instability-low. And approximately 80–90% of the patients with MSI-H could maintain sustained clinical benefits once they had an initial response. However, some patients could have primary resistance at the beginning, and some might have acquired resistance after long-term treatment. Case Presentation: We present the case of an ICC patient with MSI-H who suffered rapid progression after a short-term remission with camrelizumab, a kind of PD-1 inhibitor, as second-line treatment. The patient’s genomic and immune features were analyzed by next-generation sequencing and multiplex immunofluorescence staining to explore the possible mechanisms of the rapidly acquired resistance of ICIs in this MSI-H case. Conclusion: The genomic and immunohistochemical analysis showed that TGFBR2 mutation, loss of HLA B44 supertype, carrying B62 supertype, and increased PD-L1+ cells, macrophages, and Tregs in the tumor microenvironment might be related to the nonsustain benefit of ICIs in this MSI-H patient.
Defibrotide plus best standard of care compared with best standard of care alone for the prevention of sinusoidal obstruction syndrome (HARMONY): a randomised, multicentre, phase 3 trial
Authors: Stephan A Grupp, Selim Corbacioglu, Hyoung Jin Kang, Takanori Teshima, Seong Lin Khaw, Franco Locatelli, Johan Maertens, Matthias Stelljes, Polina Stepensky, Paty Lopez, Vian Amber, Antonio Pagliuca, Paul G Richardson, Mohamad Mohty
Journal: The Lancet Haematology (2023)
Residual Volume versus FRC Computed Tomography Assessment of Functional Small Airway Disease in Smokers with and without Chronic Obstructive Pulmonary Disease
Authors: Alejandro P. Comellas, John D. Newell, Miranda Kirby, Jered P. Sieren, Sam Peterson, Charles Hatt, Craig J. Galban, Ella A. Kazerooni, David A. Lynch, MeiLan K. Han, Eric A. Hoffman
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Residual Volume versus FRC Computed Tomography Assessment of Functional Small Airway Disease in Smokers with and without Chronic Obstructive Pulmonary Disease ." American Journal of Respiratory and Critical Care Medicine, 207(11), pp. 1536–1539
Implementation and outcomes of dolutegravir-based first-line antiretroviral therapy for people with HIV in South Africa: a retrospective cohort study
Authors: Jienchi Dorward, Yukteshwar Sookrajh, Thokozani Khubone, Johan van der Molen, Riona Govender, Sifiso Phakathi, Lara Lewis, Christian Bottomley, Munthra Maraj, Richard J Lessells, Kogieleum Naidoo, Christopher C Butler, Rose Van Heerden, Nigel Garrett
Journal: The Lancet HIV (2023)

There are few data assessing the uptake of first-line dolutegravir among men and women living with HIV in low-income and middle-income countries, and subsequent clinical outcomes in non-trial settings. We aimed to determine dolutegravir uptake in women, and the effect of dolutegravir on clinical outcomes in routine care in South Africa.
Association of Healthful Plant-based Diet Adherence With Risk of Mortality and Major Chronic Diseases Among Adults in the UK
Authors: Alysha S. Thompson, Anna Tresserra-Rimbau, Nena Karavasiloglou, Amy Jennings, Marie Cantwell, Claire Hill, Aurora Perez-Cornago, Nicola P. Bondonno, Neil Murphy, Sabine Rohrmann, Aedín Cassidy, Tilman Kühn
Journal: JAMA Network Open (2023)

Importance Plant-based diets have gained popularity for both environmental and health reasons, but a comprehensive assessment of their quality in relation to risk of mortality and major chronic diseases is lacking. Objective To examine whether healthful vs unhealthful plant-based dietary patterns are associated with mortality and major chronic diseases among UK adults. Design, Setting, and Participants This prospective cohort study used data from adults in the UK Biobank, a large-scale population-based study. Participants were recruited between 2006 and 2010 and followed up using record linkage data until 2021; follow-up for different outcomes ranged between 10.6 and 12.2 years. Data analysis was conducted from November 2021 to October 2022. Exposures Adherence to a healthful vs unhealthful plant-based diet index (hPDI vs uPDI) derived from 24-hour dietary assessments. Main Outcomes and Measures The main outcomes were hazard ratios (HRs) and 95% CIs of mortality (overall and cause specific), cardiovascular disease (CVD [total, myocardial infarction, ischemic stroke, and hemorrhagic stroke]), cancer (total, breast, prostate, and colorectal), and fracture (total, vertebrae, and hip) across quartiles of hPDI and uPDI adherence. Results This study included 126 394 UK Biobank participants. They had a mean (SD) age of 56.1 (7.8) years; 70 618 (55.9%) were women. The majority of participants (115 371 [91.3%]) were White. Greater adherence to the hPDI was associated with lower risks of total mortality, cancer, and CVD, with HRs (95% CIs) of 0.84 (0.78-0.91), 0.93 (0.88-0.99), and 0.92 (0.86-0.99), respectively, for participants in the highest hPDI quartile compared with the lowest. The hPDI was also associated with lower risks of myocardial infarction and ischemic stroke, with HRs (95% CIs) of 0.86 (0.78-0.95) and 0.84 (0.71-0.99), respectively. By contrast, higher uPDI scores were associated with higher risks of mortality, CVD, and cancer. The associations observed did not show heterogeneity across strata of sex, smoking status, body mass index, or socioeconomic status or with polygenic risk scores (specifically with regard to CVD end points). Conclusions and Relevance The findings of this cohort study of middle-aged UK adults suggest that a diet characterized by high-quality plant-based foods and lower intakes of animal products may be beneficial for health, irrespective of established chronic disease risk factors and genetic predisposition.
Detecting Neonatal AKI by Serum Cystatin C
Authors: Xin Xu, Sheng Nie, Hong Xu, Bicheng Liu, Jianping Weng, Chunbo Chen, Huafeng Liu, Qiongqiong Yang, Hua Li, Yaozhong Kong, Guisen Li, Qijun Wan, Yan Zha, Ying Hu, Gang Xu, Yongjun Shi, Yilun Zhou, Guobin Su, Ying Tang, Yanqin Li, Licong Su, Ruixuan Chen, Yue Cao, Peiyan Gao, Shiyu Zhou, Xiaodong Zhang, Fan Luo, Ruqi Xu, Qi Gao, Fan Fan Hou
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Serum creatinine is not a sensitive biomarker for neonatal AKI because it is confounded by maternal creatinine level, gestational age, and neonatal muscle mass. In this multicenter cohort study of 52,333 hospitalized Chinese neonates, the authors proposed serum cystatin C–related criteria (CyNA) for neonatal AKI. They found that cystatin C (Cys-C) is a robust and sensitive biomarker for identifying AKI in neonates who are at an elevated risk of in-hospital mortality and that CyNA detects 6.5 times as many cases as the modified Kidney Disease Improving Global Outcomes creatinine criteria. They also show that AKI can be detected using a single test of Cys-C. These findings suggest that CyNA shows promise as a powerful and easily applicable tool for detecting AKI in neonates. Background Serum creatinine is not a sensitive biomarker for AKI in neonates. A better biomarker-based criterion for neonatal AKI is needed. Methods In this large multicenter cohort study, we estimated the upper normal limit (UNL) and reference change value (RCV) of serum cystatin C (Cys-C) in neonates and proposed cystatin C–based criteria (CyNA) for detecting neonatal AKI using these values as the cutoffs. We assessed the association of CyNA-detected AKI with the risk of in-hospital death and compared CyNA performance versus performance of modified Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. Results In this study of 52,333 hospitalized neonates in China, Cys-C level did not vary with gestational age and birth weight and remained relatively stable during the neonatal period. CyNA criteria define AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 45,839 neonates with measurements of both Cys-C and creatinine, 4513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria. Compared with neonates without AKI by both criteria, neonates with AKI detected by CyNA alone had an increased risk of in-hospital mortality (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 2.02 to 4.04). Neonates with AKI detected by both criteria had an even higher risk of in-hospital mortality (HR, 4.86; 95% CI, 2.84 to 8.29). Conclusions Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. Compared with modified KDIGO creatinine criteria, CyNA is 6.5 times more sensitive in identifying neonates at elevated risk of in-hospital mortality.
Multidimensional Analysis of Lung Lymph Nodes in a Mouse Model of Allergic Lung Inflammation following PM2.5 and Indeno[1,2,3- <i>cd</i> ]pyrene Exposure
Authors: Kwei-Yan Liu, Yajing Gao, Wenfeng Xiao, Jinrong Fu, Saihua Huang, Xiao Han, Shih-Hsien Hsu, Xiaojun Xiao, Shau-Ku Huang, Yufeng Zhou
Journal: Environmental Health Perspectives (2023)

Background: Ambient particulate matter with an aerodynamic diameter of ≤2.5 μm (PM2.5) is suggested to act as an adjuvant for allergen-mediated sensitization and recent evidence suggests the importance of T follicular helper (Tfh) cells in allergic diseases. However, the impact of PM2.5 exposure and its absorbed polycyclic aromatic hydrocarbon (PAHs) on Tfh cells and humoral immunity remains unknown. Objectives: We aimed to explore the impact of environmental PM2.5 and indeno[1,2,3-cd]pyrene (IP), a prominent PAH, as a model, on Tfh cells and the subsequent pulmonary allergic responses. Methods: PM2.5- or IP-mediated remodeling of cellular composition in lung lymph nodes (LNs) was determined by mass cytometry in a house dust mite (HDM)-induced mouse allergic lung inflammation model. The differentiation and function of Tfh cells in vitro were analyzed by flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, chromatin immunoprecipitation, immunoprecipitation, and western blot analyses. Results: Mice exposed to PM2.5 during the HDM sensitization period demonstrated immune cell population shifts in lung LNs as compared with those sensitized with HDM alone, with a greater number of differentiated Tfh2 cells, enhanced allergen-induced immunoglobulin E (IgE) response and pulmonary inflammation. Similarly enhanced phenotypes were also found in mice exposed to IP and sensitized with HDM. Further, IP administration was found to induce interleukin-21 (Il21) and Il4 expression and enhance Tfh2 cell differentiation in vitro, a finding which was abrogated in aryl hydrocarbon receptor (AhR)-deficient CD4+ T cells. Moreover, we showed that IP exposure increased the interaction of AhR and cellular musculoaponeurotic fibrosarcoma (c-Maf) and its occupancy on the Il21 and Il4 promoters in differentiated Tfh2 cells. Discussion: These findings suggest that the PM2.5 (IP)–AhR–c-Maf axis in Tfh2 cells was important in allergen sensitization and lung inflammation, thus adding a new dimension in the understanding of Tfh2 cell differentiation and function and providing a basis for establishing the environment–disease causal relationship. https://doi.org/10.1289/EHP11580
Hepatopulmonary syndrome is associated with low sphingosine-1-phosphate levels and can be ameliorated by the functional agonist fingolimod
Authors: Sukriti Baweja, Anupama Kumari, Preeti Negi, Arvind Tomar, Dinesh Mani Tripathi, Akash Kumar Mourya, Aayushi Rastogi, P. Debishree Subudhi, Swati Thangariyal, Guresh Kumar, Jitendra Kumar, G. Srinivasa Reddy, Arun Kumar Sood, Chitranshu Vashistha, Vivek Sarohi, Chhagan Bihari, Rakhi Maiwall, Shiv Kumar Sarin
Journal: Journal of Hepatology (2023)
Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers
Authors: Joëlle A. Pasman, Joeri J. Meijsen, Marit Haram, Kaarina Kowalec, Arvid Harder, Ying Xiong, Thuy-Dung Nguyen, Andreas Jangmo, John R. Shorter, Jacob Bergstedt, Urmi Das, Richard Zetterberg, Ashley Tate, Paul Lichtenstein, Henrik Larsson, Ingvild Odsbu, Thomas Werge, Ted Reichborn-Kjennerud, Ole A. Andreassen, Patrick F. Sullivan, Alfonso Buil, Martin Tesli, Yi Lu
Journal: The Lancet Regional Health - Europe (2023)

Major depressive disorder (MDD) is a common psychiatric disorder associated with a high disease burden. This study gives a comprehensive overview of the prevalence, outcomes, treatment, and genetic epidemiology of MDD within and across the Scandinavian countries.This study has aimed to assess and compare across Norway, Denmark, and Sweden 1) the prevalence and trajectories of MDD and comorbidity, 2) outcomes and treatment, and 3) heritability (Denmark and Sweden only). The analyses leveraged data on 272,944 MDD cases (and 6.2 million non-cases) from Norway, Sweden, and Denmark in specialist care in national longitudinal health registers covering 1975-2013. Relying on harmonized public data global comparisons of socioeconomic and health metrics were performed to assess to what extent findings are generalizable.MDD ranked among the most prevalent psychiatric disorders. For many cases, the disorder trajectory was severe, with varying proportions experiencing recurrence, developing comorbid disorders, requiring inpatient treatment, or dying of suicide. Important country differences in specialist care prevalence and treatment were observed. Heritability estimates were moderate (35-48%). In terms of socioeconomic and health indices, the Scandinavian nations were comparable to one another and grouped with other Western nations.The Scandinavian countries were similar with regards to MDD epidemiological measures, but we show that differences in health care organization need to be taken into consideration when comparing countries. This study demonstrates the utility of using comprehensive population-wide registry data, outlining possibilities for other applications. The findings will be of use to policy makers for developing better prevention and intervention strategies.Swedish Research Council (Vetenskapsrådet, award D0886501 to PFS), US National Institutes of Mental HealthR01 MH123724 (to PFS), European Union's Horizon 2020 Research and Innovation Program (847776 and 964874, to OA) and European Research Council grant (grant agreement ID 101042183, to YL).
Economic evaluations of interventions to prevent and control health-care-associated infections: a systematic review
Authors: Stephen Rice, Katherine Carr, Pauline Sobiesuo, Hosein Shabaninejad, Giovany Orozco-Leal, Vasileios Kontogiannis, Christopher Marshall, Fiona Pearson, Najmeh Moradi, Nicole O'Connor, Akvile Stoniute, Catherine Richmond, Dawn Craig, Benedetta Allegranzi, Alessandro Cassini
Journal: The Lancet Infectious Diseases (2023)
Activation of inflammasomes and their effects on neuroinflammation at the microelectrode-tissue interface in intracortical implants
Authors: Melissa E. Franklin, Cassie Bennett, Maelle Arboite, Anabel Alvarez-Ciara, Natalie Corrales, Jennifer Verdelus, W. Dalton Dietrich, Robert W. Keane, Juan Pablo de Rivero Vaccari, Abhishek Prasad
Journal: Biomaterials (2023)
An immunometabolism subtyping system identifies S100A9+ macrophage as an immune therapeutic target in colorectal cancer based on multiomics analysis
Authors: Xuanwen Bao, Danyang Wang, Xiaomeng Dai, Chuan Liu, Hangyu Zhang, Yuzhi Jin, Zhou Tong, Bin Li, Chuchu Tong, Shan Xin, Xin Li, Yanfang Wang, Lulu Liu, Xudong Zhu, Qihan Fu, Yi Zheng, Jingwen Deng, Weihong Tian, Tiannan Guo, Peng Zhao, Wenbin Chen, Weijia Fang
Journal: Cell Reports Medicine (2023)

Immunometabolism in the tumor microenvironment (TME) and its influence on the immunotherapy response remain uncertain in colorectal cancer (CRC). We perform immunometabolism subtyping (IMS) on CRC patients in the training and validation cohorts. Three IMS subtypes of CRC, namely, C1, C2, and C3, are identified with distinct immune phenotypes and metabolic properties. The C3 subtype exhibits the poorest prognosis in both the training cohort and the in-house validation cohort. The single-cell transcriptome reveals that a S100A9+ macrophage population contributes to the immunosuppressive TME in C3. The dysfunctional immunotherapy response in the C3 subtype can be reversed by combination treatment with PD-1 blockade and an S100A9 inhibitor tasquinimod. Taken together, we develop an IMS system and identify an immune tolerant C3 subtype that exhibits the poorest prognosis. A multiomics-guided combination strategy by PD-1 blockade and tasquinimod improves responses to immunotherapy by depleting S100A9+ macrophages in vivo.